title: Cumulative exposure to cell-free HIV in breast milk, rather than feeding pattern per se, identifies postnatally infected infants.
abstract: BACKGROUND
  We quantified the relationship between human immunodeficiency virus (HIV) RNA shedding in breast milk, cumulative RNA exposure, and postnatal transmission, relating timing of infection in the infant to estimated total volume of milk exposure.
  
  
  METHODS
  Nested case-control study of 36 infants of HIV-infected mothers. Case patients were infants who acquired HIV infection through breastfeeding from age 6 through 28 weeks, and control subjects were uninfected infants matched on age at obtainment of a breast milk sample. Mothers and infants received peripartum single-dose nevirapine prophylaxis. Feeding data were collected daily; breast milk samples were collected and infant anthropometry was performed at 6 weeks and monthly thereafter. Volume of milk ingested was estimated using infant weight and feeding pattern.
  
  
  RESULTS
  Before HIV acquisition in case patients, feeding pattern (exclusive breastfeeding; median duration, 65 vs 70 days; P = .6) and daily milk intake (mean volume, 638 vs 637 mL; P = .97) did not differ significantly between case patients and control subjects. Case mothers were more likely to shed virus (64% vs 9% always, 22% vs 20.5% intermittently, 14% vs 70.5% never shed; overall, P < .001). Case patients ingested ~15 times more HIV-1 RNA particles than did control subjects (196.5 vs 13 × 10⁶ copies; P < .001). Allowing for maternal antenatal CD4 cell count and plasma HIV-1 load, child sex and duration of mixed breastfeeding, the association between HIV RNA exposure and infection remained statistically significant (P < .001).
  
  
  CONCLUSIONS
  Postnatal acquisition of HIV-1 is more strongly associated with cumulative exposure to cell-free particles in breast milk than with feeding mode. Reducing breast milk viral load through antiretroviral therapy to mother or child can further decrease postnatal transmission in exclusively breastfed infants.
authors.affiliation: Département d'Information Médicale et Laboratoire de Bactériologie-Virologie, Université Montpellier 1, EA 4205 and CHU Montpellier, Montpellier, France.
authors.forename: Dorine
authors.initials: D
authors.lastname: Neveu
authors.forename: Johannes
authors.initials: J
authors.lastname: Viljoen
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Bland
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
authors.forename: Siva
authors.initials: S
authors.lastname: Danaviah
authors.forename: Anna
authors.initials: A
authors.lastname: Coutsoudis
authors.forename: Nigel Campbell
authors.initials: NC
authors.lastname: Rollins
authors.forename: Hoosen M
authors.initials: HM
authors.lastname: Coovadia
authors.forename: Philippe
authors.initials: P
authors.lastname: Van de Perre
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Newell
mesh_terms: D000328:Adult; D000886:Anthropometry; D019380:Anti-HIV Agents / Q000008:administration & dosage; D016022:Case-Control Studies; D018890:Chemoprevention / Q000379:methods; D005247:Feeding Behavior; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000635:transmission*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008895:Milk, Human / Q000821:virology*; D019829:Nevirapine / Q000008:administration & dosage; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D017201:Virus Shedding
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D019829:Nevirapine